The objective of our current research is to dissect the genetic control of human cell surface functions with emphasis on the receptors for bioactive polypeptides, insulin and epidermal growth factor. Attempts are being made to identify the genes responsible for production and regulation of the active receptor molecules and of the regulatory enzymes and factors involved in the corresponding metabolic pathways; to understand the genetic variation in the receptor molecules and their effects on the functions of metabolic enzymes; to assign these genes to specific human chromosomes and localize them to specific regions of the chromosomes; and to understand coordination and/or hierarchy of gene action in the receptor-mediated hormonal signal transfer mechanisms. We have been using somatic cell genetic approaches to achieve these goals in combination with biochemical and immunological techniques. Attempts are being made to isolate a series of genetically altered mutant cells, which are defective in each of the components essential for hormone action and for further specific steps in the signal transfer and in the metabolic sequences controlled, from in vitro mutagenized cell populations. Intra- and interspecific cell hybrids will be produced in various combinations of mutant cells and wild type cells from human and mouse origins.